[Atlas] Add pathway diagrams to 20 hypotheses missing mechanism maps open analysis:6 reasoning:6

Goal

Add pathway or mechanism diagrams to active hypotheses with empty pathway_diagram fields. Mechanism maps make hypotheses inspectable and connect Agora claims to Atlas pathway context.

Acceptance Criteria

Approach

Select hypotheses with target gene, target pathway, or evidence-rich descriptions and empty pathway diagrams.

Build compact mechanism diagrams from existing KG edges, citations, and hypothesis text.

Validate diagram syntax and update the hypothesis rows.

Verify hypothesis detail pages still render.

Dependencies

• 58230ac8-c32 - Atlas quest

Dependents

• Hypothesis inspection, Atlas entity context, and pathway-aware debates

Work Log

2026-04-27 - Slot claude-auto:41 - Task f0d1db67 backfill: 15 hypotheses, all new diagrams

• Staleness check: 0 active hypotheses missing pathway_diagram (all 24 active hypotheses have diagrams).

Prior agents have completed coverage for active/promoted/debated statuses. Remaining missing:
open=3, proposed=113 (non-archived total=116).

• Targeted top 15 proposed/open hypotheses by composite_score with no existing diagram.
• Created backfill/backfill_pathway_diagrams_f0d1db67.py with 15 mechanistically specific diagrams:

- P2RX7/NLRP3: Trazodone P2X7 antagonism → NLRP3 inhibition → reduced IL-1beta neuroinflammation
- HLA/CD8/RIPK3/MLKL: Paraneoplastic CD8+ CTL recognition → necroptosis → myelopathy
- MT1/CHOP: High-dose melatonin MT1 receptor → PERK/CHOP suppression → Abeta42 neuroprotection
- eIF2alpha/ATF4: Low-dose trazodone → p-eIF2alpha reduction → ATF4/CHOP suppression → stress resilience
- CD47/SIRPa: CD47 "don't eat me" → SIRPa/PTPN6/PTPN11 checkpoint → amyloid accumulation; blockade enables clearance
- 2-HG/KDM4B: alpha-KG/2-HG balance → KDM4B inhibition → H3K9me3 persistence → epigenetic window
- SPP1/RAGE/STAT3: Abeta → RAGE → NF-kB → IL-6 → STAT3 → SPP1 autocrine loop in perivascular fibroblasts
- BCHE/ACHE/GSK3B: Reactive astrocytes → cholinesterase overexpression → ACh deficit → GSK3B → tau phosphorylation
- KLF4/P2RY12: KLF4 transcriptional repression of P2RY12 → impaired microglial chemotaxis
- G3BP1/CK2: CK2 hyperphosphorylation of G3BP1 → TRIM21 access blocked → toxic stress granule persistence
- DNMT1/TET2/P2RY12: Aging → DNMT1/TET2 dysregulation → P2RY12 promoter hypomethylation → microglial identity loss
- FFAR3/STAT3: Gut dysbiosis → propionate deficiency → FFAR3 loss → STAT3 anti-inflammatory failure
- Gut/LPS/TMAO/HDAC6: Gut dysbiosis → LPS/TMAO → HDAC6 microglial priming → NF-kB neuroinflammation; FMT resets
- FUS/G3BP1: FUS mutation → cytoplasmic mislocalization → G3BP1 chaperone impairment → toxic SG intermediates
- PARP1/ATM/XRCC1/LIG3: DNA damage → PARP1/ATM/XRCC1/LIG3 BER deficiency → TDP-43 stress → feed-forward loop

• Pre-validated all 15 diagrams with validate_mermaid() — 0 failures.
• Executed backfill: before=115, Updated=15, skipped=0, after=100 (net -15).
• Spot-check render: h-32a6b226a4, h-f5518156, h-b4bec30ca0, h-4c4bf4a28f, h-a3a9b0941b all HTTP 200.
• Wiki page check: none of the 15 hypotheses have linked wiki pages (no wiki updates needed).
• Missing count reduced: 115 → 100 for proposed/open/active.

2026-04-26 23:55 PDT - Slot minimax:74 - Task 9fc63687 backfill: 7 hypotheses, all new diagrams

• Staleness check: only 2 active hypotheses remain missing (was 135+ at task start), but 176 proposed/open/active missing in total.
• Created backfill/backfill_pathway_diagrams_9fc63687.py targeting top missing by score.
• Added 7 new mechanism-specific Mermaid flowchart diagrams with SciDEX color coding:

- Multi-Clock IDS (PD): epigenetic clock ensemble divergence → IDS → PD prodromal signal
- GrimAge CSF (AD): GrimAge acceleration + CSF cell-type deconvolution → early AD stratification
- TREM2: TREM2-deficient microglia → DAM failure → amyloid plaque accumulation → cognitive decline
- LRRK2 (amplified): amplified pathological signaling → lysosomal dysfunction → therapeutic window
- C1Q: complement C1Q → synaptic pruning → early cognitive decline
- NUP98 (C9orf72 DPR): DPR proteins → NUP98 impairment → nucleocytoplasmic transport blocked → proteostatic stress
- LRRK2/RAB29: G2019S → RAB29 recruitment → enhanced lysosomal volume sensing → neuronal death

• Pre-validated all 7 diagrams with validate_mermaid() — 0 failures.
• Executed backfill: before=176, Updated=7, skipped=0, after=169 (net -7).
• All 7 spot-check hypotheses returned HTTP 200 at /hypothesis/<id>.
• Missing count reduced: 176 → 169 for proposed/open/active.

2026-04-26 21:42 PDT - Slot claude-auto:45 - Task 55a2bfc5 backfill: 20 hypotheses, all new diagrams

• Confirmed task still live: 135 hypotheses (non-test, non-spark) with target_gene missing pathway_diagram.
• Created generate_pathway_diagrams.py targeting the top 20 by composite_score (excluding hyp_test/h-spark prefixes).
• Added 20 new mechanism-specific Mermaid flowchart diagrams with SciDEX color coding:

- NCOA4: FUS mutation → mitochondrial dysfunction → oxidative stress → NCOA4-mediated ferritinophagy → labile iron → lipid peroxidation → ferroptosis (FUS-ALS)
- AD/IL/TNF: Hispanic/Latino epigenetic clock divergence → neuroinflammation CpG methylation → IL/TNF attenuation → amyloid-tau decoupling → cognitive resilience
- P2RY12: VSMC foam cells → PDGF-BB/VEGF imbalance → pericyte detachment → BBB breakdown → neurovascular uncoupling
- CHIP/STUB1: Misfolded tau/APP → Hsp70 → CHIP E3 ligase → polyubiquitination → proteasomal clearance
- SREBF2: APOE4 reactive glia → NF-kB/mTORC1 → SCAP-SREBP2 → cholesterol biosynthesis dysregulation
- CX3CL1/CX3CR1: Fractalkine → CX3CR1 microglial → PI3K/Akt → homeostatic surveillance → synaptic protection
- IGFBPL1: Intranasal → olfactory transport → hippocampal/cortical IGF signaling → neuroprotection
- C1QA/C1QC: Cardiovascular risk → complement C1QA/C1QC → glial activation → synapse pruning → vascular dementia
- HIF1A: HBOT 1.5-2.0 ATA → sub-lethal ROS → paradoxical HIF-1alpha stabilization → VEGF → angiogenesis → perfusion
- MCU/CK1D/GSK3B/PARP1: Mitochondrial dysfunction → MCU calcium dysregulation → stress kinases → TDP-43 phosphorylation → aggregation
- CD44/SRC/PI3K/MTOR: SPP1 → CD44 → SRC → PI3K/AKT → MTOR → cytoskeletal remodeling → phagocytosis
- ATP6V0C/ATP6V1: Trehalose osmotic trapping → lysosomal swelling → V-ATPase inhibition → alkalinization → TFEB → biogenesis
- BAG3: Synaptic protein misfolding → Hsc70 → BAG3 → p62/SQSTM1 → selective autophagy → proteostasis
- TREM2 (APOE/TREM2): Aging → APOE lipoprotein → TREM2 lipid sensing → DAM transition failure → plaque accumulation → AD
- SPP1 (perivascular): Perivascular SPP1 → CD44/integrin → pericyte dysfunction → BBB breakdown → amyloid → cognitive decline
- SST/CREB1/lncRNA-9969: Alpha-beta oscillations → SST interneuron → CREB1 → lncRNA-9969 → ceRNA → autophagy induction
- ST3GAL5: ST3GAL5 activation → GM3/GD3 synthesis → reduced GM1 → lipid raft remodeling → BACE1 attenuation → fewer Abeta seeds
- HDAC1: Early amyloid → HDAC1 epigenetic priming → DAM signature → TREM2-dependent DAM transition
- TYROBP/SYK: TYROBP/DAP12 hub → SYK → MAPK/ERK → sustained microglial hyperactivation → neurodegeneration point of no return
- SQSTM1/CALCOCO2: Stress → LLPS stress granule → saturation partitioning → SQSTM1/CALCOCO2 exclusion from SG core → failed selective autophagy

• Pre-validated all 20 diagrams with validate_mermaid() — 0 failures before DB write.
• Applied SciDEX color coding: blue=mechanisms (fill:#1a237e), red=pathology (fill:#b71c1c), green=therapeutics (fill:#1b5e20).
• Executed backfill: Updated=20, skipped=0 (committed via PGShimConnection context manager).
• Post-validate: 20/20 PASS from stored DB diagrams.
• Missing count reduced: ~135 → ~115 (proposed/open/active with target_gene).

2026-04-26 08:11 PDT - Slot 44 (claude-auto:44) - Task 7abb6155 backfill: 15 hypotheses, 4 new diagrams

• Confirmed task still live: 306 hypotheses with pathway_diagram IS NULL total (188 proposed, 110 archived, 4 active, 4 open).
• Created backfill/backfill_pathway_diagrams_7abb6155.py targeting the top 15 by composite_score (no status filter, includes 1 archived row).
• Added 4 new mechanism-specific Mermaid diagrams:

- PDHA1: Hybrid glycolysis/OXPHOS metabolic state in primed microglia (pyruvate dehydrogenase complex)
- PKM2: PKM2 nuclear translocation → H3-T11 phosphorylation, HIF1alpha co-activation, STAT3 → pro-inflammatory transcription
- BACE1: BACE1/GSK3beta amyloid-tau synergistic reduction (secondary therapeutic effect cascade)
- CD47: Anti-CD47/SIRPalpha checkpoint blockade → microglial phagocytic clearance of amyloid

• All 4 new diagrams pre-validated with validate_mermaid() — 0 failures.
• Also fixed false-positive 'AR' key match for CD47/SIRPalpha hypothesis by using full-word boundary regex in alias lookup.
• Executed backfill: Updated=15 skipped=0. All 15 get both pathway_diagram and updated content_hash.
• After: 291 total NULL pathway_diagram; 182 proposed/open/active missing.
• Hypotheses updated: h-703a747d3b (LMNB1), h-42d01f0454 (KL), h-591d641a01 (PDHA1), h-2f032e79df (AIF1), h-98ddffb4cd (PKM2), h-6ca2dbc5f0 (REST), h-1e2b7f1c (VPS35), SDA-...-H007 (NLGN1, archived), h-4898d2a838 (TFEB), h-cf07e38ecd (BACE1), h-929aef3ac1 (G3BP1), h-177d9cb05108 (CHI3L1), h-562d178a (CD47), h-1487c2bad4 (TGFBR1), h-f3eff15058ab (MAP6).
• Final validate_mermaid check on all 15 stored DB diagrams: 15/15 PASS, 0 failures.
• Spot-check render: /hypothesis/h-591d641a01, /hypothesis/h-98ddffb4cd, /hypothesis/h-562d178a, /hypothesis/h-cf07e38ecd all returned HTTP 200.

2026-04-26 14:26 PDT - Slot claude-auto:43 - Task c15f66ad backfill: 25 hypotheses, 10 new diagrams for gap-hypothesis patterns

• Confirmed task still live: 159 hypotheses in status IN ('proposed','open','active') missing pathway_diagram (threshold < 20 chars).
• Noted 18 new active "gap" hypotheses created at 14:17 PDT with descriptive target_gene values (e.g. "age-linked CpG drift", "tight-junction remodeling", "TLR4 priming") not matched by existing library.
• Added 10 new mechanism-specific Mermaid diagrams:

- TLR4: Gut dysbiosis → LPS translocation → TLR4/MyD88/NF-κB → microglial priming → neurodegeneration
- CpG_DRIFT: Age-linked CpG hypomethylation → DNMT1 failure + transposon derepression → cGAS-STING + SASP → glial identity drift
- BBB_TJ: Tight-junction CLDN5/OCLN complex → ZO-1 scaffold dissociation → claudin internalization → BBB leakage
- PLASMA_GFAP: Pericyte stress → astrocyte reactivity → GFAP upregulation/release (plasma biomarker) → neuronal vulnerability
- ATAC_CHROM: ATAC-seq chromatin accessibility → cell-type regulatory landscapes → aging-associated enhancer loss → causal mechanism discrimination
- ENDO_TRANS: Caveolae-mediated endothelial transcytosis → intracellular trafficking → pathological vs therapeutic delivery
- PROT_CHROM: Protective chromatin remodeling (H3K27ac/H3K9me3) → stage-dependent transition → early intervention window
- NCOA4: NCOA4 ferritinophagy → lysosomal iron release → Fenton/lipid peroxidation → ferroptosis (FUS-ALS context)
- PTK2B: PTK2B kinase/calcium → autophosphorylation → PICALM endocytosis → BIN1 membrane tubulation → tau seed propagation
- ABI3: TREM2/DAP12 → SYK → ABI3/WAVE complex → Arp2/3 → phagocytic clearance (TREM2-ABI3 convergent AD axis)

• Added new EXTRA_ALIASES: TLR4 (LPS, SCFA, MICROBIOME, DYSBIOSIS, BUTYRATE), CpG_DRIFT (CPG), BBB_TJ (TIGHT-JUNCTION), PLASMA_GFAP (GFAP, PERICYTE), ATAC_CHROM (ATAC), ENDO_TRANS (TRANSCYTOSIS), PROT_CHROM (PROTECTIVE CHROMATIN word-boundary), NCOA4 (FERRITINOPHAGY), INFLAMMASOME→NLRP3 (for microglial inflammasome tone matching).
• Pre-validated all 10 new diagrams with validate_mermaid() — 0 failures.
• Executed backfill: before=159, Updated=25, skipped=0, after=134.
• Hypotheses updated: h-gap-92152803-m1/m2/m3 (generic), h-gap-5c6cec3e-m1 (BBB_TJ), h-gap-e7852b55-m1 (CpG_DRIFT), h-gap-456a357b-m1 (CpG_DRIFT), h-gap-2f2e5b80-m1 (TLR4), h-gap-5c6cec3e-m2 (PLASMA_GFAP), h-gap-e7852b55-m2 (ATAC_CHROM), h-gap-456a357b-m2 (ATAC_CHROM), h-gap-2f2e5b80-m2 (TLR4 via LPS), h-gap-5c6cec3e-m3 (ENDO_TRANS), h-gap-e7852b55-m3 (PROT_CHROM), h-gap-456a357b-m3 (PROT_CHROM), h-gap-2f2e5b80-m3 (NLRP3 via INFLAMMASOME), h-gwas-plcg2 (PLCG2), h-gwas-trem2-abi3 (TREM2), h-gwas-ptk2b (PTK2B), h-00073ccb (generic), h-e91a4dd06a (FSP1), h-2b95e7ad70 (EV_BIOGEN), h-df4e435ebf (TARDBP), h-41b54533e6 (AIF1), h-896e71b129 (PDGFRB), h-cb2065e26c (CGAS).
• Post-validate: 25/25 PASS from stored DB diagrams.
• Spot-check render: h-gap-5c6cec3e-m1, h-gap-e7852b55-m1, h-gap-2f2e5b80-m1, h-gwas-ptk2b, h-gwas-plcg2 all HTTP 200.
• Missing count reduced: 159 → 134 (net -25).

2026-04-26 12:54 PDT - Slot claude-auto:47 - Task 6bd175aa backfill: 20 hypotheses, 6 new diagrams + word-boundary fix

• Confirmed task still live: 161 hypotheses in status IN ('proposed','open','active') missing pathway_diagram (threshold < 20 chars).
• Identified 6 gene targets not covered by the 249-key merged library from iter6: OPA1/DRP1/DNM1L (mitochondrial cristae dynamics), KIF5B/KIF5C (kinesin anterograde transport), USP14 (deubiquitinase at 19S proteasome), ECEPs/PAX6-AS1/KCNC2-AS1 (enhancer-linked lncRNAs), EV biogenesis/GW4869 (astrocyte extracellular vesicle), miRNA/ceRNA competition (mmu-miR-6361).
• Created backfill/backfill_pathway_diagrams_6bd175aa.py with 6 new mechanism-specific Mermaid diagrams.
• Restored word-boundary alias matching (regression fix: iter6 dropped \b guard from iter7abb6155, causing false positives — "AR" matching "Architecture", "CLU" matching "Exclusion").
• Pre-validated all 6 new diagrams with validate_mermaid() — 0 failures.
• Executed backfill: before=161, Updated=20, skipped=0, after=141.
• All 20 hypotheses received mechanistically specific diagrams (0 generic fallbacks).
• Hypotheses updated: h-65b79f09 (APOE), h-3294f3a8 (CCR2), h-f9e4985929 (TREM2), h-098b03f430 (MIRNA_CERNA), h-a0bd8d4f4c (GRIN2B), h-588406cca9 (TARDBP), h-6be018d35a (AR), h-373fac84b5 (P2RY12), h-c40be3e018 (OPA1 — was false AR match), h-23cba4e15d (AQP4), h-0c68c97b58 (NPTX2), h-6f6f920e83 (SNCA), h-4682ee7fdf (ADORA2A), h-a976bf02b0 (ECEP — was false AR match), h-4b91b4b2d5 (TARDBP), h-3a0c21057e (KIF5B — was false CLU match), h-7ed5dae4 (TDP, active), h-43a8ab92dd (SIRT3), h-92a69aa3 (USP14), h-7856aa8a (SIRT1).
• Post-validate: 20/20 PASS from stored DB diagrams.
• Spot-check render: h-098b03f430, h-c40be3e018, h-a976bf02b0, h-3a0c21057e, h-92a69aa3 → all HTTP 200.
• Missing count reduced: 161 → 141 (net -20).

2026-04-26 13:22 PDT - Slot minimax:70 - Iteration 6 backfill: 20 hypotheses, 17 new mechanism diagrams

• Confirmed task still live: 216 hypotheses in status IN ('proposed','open','active') missing pathway_diagram (threshold < 20 chars).
• Analyzed top 25 missing hypotheses (by composite_score). Identified 12 gene targets not yet in the 245-key merged library: TNFAIP2 (TNT formation), NUP107 (nucleoporin), LMNB1 (Lamin B1), HDAC1/2 (histone deacetylase complex), REST (neuronal transcription factor), AIF1/IBA1 (microglial marker), C1Q (complement), SPP1 (osteopontin), CLU (clusterin), DGAT1 (acyltransferase), KLF4 (Kruppel-like factor), ITGAX/CD11c (dendritic integrin), PTN (pleiotrophin), GPC1 (glypican-1), PPP2R2B (PP2A regulatory), KL (Klotho).
• Created backfill/backfill_pathway_diagrams_8592c56e_iter6.py with 17 new mechanism-specific Mermaid diagrams (TNFAIP2 TNT signaling, NUP107 NPC, LMNB1 nuclear envelope senescence, HDAC1/2 epigenetic regulation, REST neuronal silencing, AIF1/IBA1 microglial, C1Q complement cascade, SPP1 osteopontin signaling, CLU clusterin chaperone, DGAT1 triglyceride synthesis, KLF4 reprogramming, ITGAX CD11c integrin, PTN pleiotrophin, GPC1 glypican-1, PPP2R2B PP2A, KL Klotho anti-aging).
• Pre-validated all 17 new diagrams with validate_mermaid() — 0 failures before DB write.
• Executed backfill: before=216, Updated=20, skipped=0, after=196. Hypotheses updated: h-b08fbcfeb6 (KLF4), h-4b6e8204bf (APOE), h-afa87d4671 (TNFAIP2), h-76e3baa925 (NUP107), h-6c20b3450d (HDAC1), h-bc10d5f3fd (ITGAX), h-3b463f9c27 (SPP1), h-ec9e48df (NFE2L2), h-15aa6d36c0 (NFE2L2), h-aging-h5-regional-vuln (CLU), h-455dbebe (DGAT1), h-05e92f66f1 (TAU), h-a3bfd2e13a (AR), hyp_test_0215075b (TREM2), h-c1aec6a4 (PPP2R2B), h-5d68a7d2 (TREM2), h-2b25f4433e (MAPT), h-7478dba3ed (PTN), h-f94e391387 (C1Q), h-848a3f33cc (GPC1).
• Missing count reduced: 216 -> 196 (net -20).
• Committed: 8ef282954.

2026-04-26 05:25 PDT - Slot 44 (claude-auto:44) - Iteration 5 backfill: 20 hypotheses, 6 new mechanism diagrams

• Confirmed task still live: 256 hypotheses in status IN ('proposed','open','active') missing pathway_diagram (threshold < 20 chars).
• Analyzed top 20 missing hypotheses (by composite_score). Identified 6 gene targets not yet in the 229-key merged library: TSPO, TNFRSF12A (M-Sec), MIR155, POLYCOMB (PRC2/EZH2 switch), PDGFRalpha, FERROPTOSIS (GSH/peroxynitrite convergent).
• Created backfill/backfill_pathway_diagrams_26508f0d_iter5.py with 6 new mechanism-specific Mermaid diagrams (TSPO mitochondrial neuroinflammation, TNFRSF12A tunneling nanotube propagation, MIR155 microglial priming, POLYCOMB PRC2-to-Trithorax synaptic switch, PDGFRalpha OPC differentiation, FERROPTOSIS GSH-depletion cascade).
• Pre-validated all 6 new diagrams with validate_mermaid() — 0 failures before DB write.
• Executed backfill: before=256, Updated=20, skipped=0, after=236. Hypotheses updated: h-0516c501 (TFEB), h-a947032c (MCT1), h-5c9b3fe9 (POLYCOMB), h-56a149a41c (FERROPTOSIS), h-658167b004 (VCP), h-d083850487 (TREM2), h-ecfaa2cbb2 (ADORA2A), h-c98d1cb4e7 (RGS6), h-851ef04ad8 (MAPT), h-2842eb0a8b (C1QA), h-0ba5108157 (PDGFRA), h-428057939b (TNFRSF12A), h-e9c2d00456 (EZH2), h-2a31d5df00 (TSPO), h-ebf902e71c (PIK3C3), h-fcd35131cf (C1QA), h-26d64f6a47 (C1R), h-c381434159 (MIR155), h-115a27fb8c (DNMT1), h-64e3588957 (TREM2).
• Missing count reduced: 256 -> 236 (net -20).

2026-04-26 03:30 PDT - Slot 52 (codex) - Iteration 4 backfill: 20 more hypotheses, 29 new mechanism diagrams

• Confirmed task still live before work: 296 hypotheses in status IN ('proposed','open','active') missing pathway_diagram.
• Analyzed 30 top-scoring missing hypotheses to identify genes needing new diagram coverage. Found 31 gene targets not yet in the merged diagram library (200 keys from prior iterations): ADORA2A, AR, BAG3, CHRM1, CREB1, CSNK2A1, DNAJC7, DNMT1, FDXR, FMRP, FSP1, HuR, IL6R, ITGB1, JAK1, METTL14, NEAT1, NFE2L2, NLGN1, NQO1, OLR1, P2RY12, RGS6, SENP1, SLC15A2, SNAP25, SYP, TIA1, YTHDC1.
• Created backfill/backfill_pathway_diagrams_79f0e94b_iter4.py with 29 new mechanism-specific Mermaid diagrams covering all identified missing targets.
• Validated all 29 new diagrams with validate_mermaid() — 0 failures before DB write.
• Executed backfill: before=276, Updated=20, skipped=0, after=256. Hypotheses updated: h-8a1a418d72 (APP), h-a0a251cfcf (NLRP3), h-10ac959b07 (AR), h-6298061b6e (AR), h-99dd982b52 (NQO1), h-2a43bfc5b1 (SPP1), h-8ebce483d2 (NFE2L2), h-6ae3f31128 (APOE), h-cbd5cd6b7f (BAG3), h-758b4994eb (SPP1), h-389692c80b (TAU), h-0d030c455b (STAT3), h-fa757ac897 (SNCA), h-23b49dc7d3 (53BP1), h-5669af0f (TDP), hyp_test_490ced0b (TREM2), h-94e73015 (AR), h-ae4a2281 (AR), h-0a1650e6 (AMYLOID), h-59d95760 (MAPT).
• Committed a572d9124 and pushed to origin/orchestra/task/79f0e94b-add-pathway-diagrams-to-20-hypotheses-mi.
• Missing count reduced: 296 -> 256 (net -40 across iterations 3+4 this slot).

2026-04-26 03:29 PDT - Slot 52 (codex) - Iteration 3 current-slice backfill + mechanism coverage expansion

• Re-ran the staleness check against live PostgreSQL before editing: 296 hypotheses in status IN ('proposed', 'open', 'active') still had empty/short pathway_diagram values, so the task remained live.
• Extended backfill/backfill_pathway_diagrams_79f0e94b_iter3.py with six new mechanism-specific Mermaid diagrams for the current top missing slice: NRXN1/NLGN1/C1q synapse tagging, CYP46A1 cholesterol efflux, OSKM late-stage epigenetic reset, TOM20/TOM40 mitochondrial import fidelity, hs-CRP -> IL-1beta inflammatory amplification, and lncRNA-0021 / miR-6361 structural sequestration; also added the exact alias hooks needed for these live targets.
• Executed python3 backfill/backfill_pathway_diagrams_79f0e94b_iter3.py against PostgreSQL and updated 20 proposed hypotheses with validated flowchart TD pathway diagrams: h-9e877c49ba, h-d12d82fb56, h-80d39d9095, h-ad2607a5c9, h-1dd95a85f3, h-a3998f0e46, h-5b6ec35742, h-811f3e6d09, h-65d6aa9d6c, h-2ae232e9fa, h-25be864e, h-292a1ec3, h-6636218992, SDA-2026-04-02-gap-tau-prop-20260402003221-H006, h-9d2bca0f28, h-9cd3aac2, h-909ba8c750, h-c1f19a34, h-9ec34d6f, and h-49112ee4c0.
• Before/after missing count for the in-scope statuses moved 296 -> 276 (Updated=20 skipped=0 net=20). Direct DB re-check confirmed all 20 stored diagrams begin with flowchart TD and validate_mermaid() reported 0 failures.
• Verification: python3 -m py_compile backfill/backfill_pathway_diagrams_79f0e94b_iter3.py passed; python3 -m pytest tests/test_hypothesis_pathway_diagrams.py -q passed (1 passed); hypothesis detail renders for h-9e877c49ba, h-2ae232e9fa, h-9cd3aac2, h-c1f19a34, and h-49112ee4c0 all returned HTTP 200 and included the Curated Mechanism Pathway Mermaid block.

2026-04-26 03:16 PDT - Slot minimax:70 - Iteration 3 backfill + library expansion

• Pre-work staleness check: 376 hypotheses still missing pathway diagrams (live PostgreSQL count), confirming task is not stale.
• Identified 26 genes in top-30 missing that had no diagram library coverage: TNF, STAT3, KCNJ10, CCR2, STUB1, HSPA8, SARM1, DNAJB6, CD38, GJA1, ESR1, REST, ATG14L, UVRAG, NRBF2, RAB35, JIP4, ALOX15, SELENOP, 53BP1, PSMD4, RIF1, VCP, plus IKBKB/HDAC6/HPRT1/NAMPT aliases.
• Added 26 new mechanism-specific Mermaid diagrams covering neurodegeneration-relevant biology for each gene.
• Validated all 26 new diagrams with validate_mermaid.py (all valid=True before DB write).
• Ran backfill: 2 batches, 40 hypotheses updated (376 -> 336 -> 316 remaining).
• New hypotheses enriched include REST, GJA1, ESR1, RELA, 53BP1, CLDN5, NAMPT, NLRP3, MTOR, SIRT3, TREM2, EZH2.
• Committed: b1a5ffac4 (expanded library + check_missing helper + 2-batch backfill).
• After rebase onto latest remote, pushed 48872438d to origin.
• Remaining missing (active/proposed/open): 316, down from 527 at task start.

2026-04-26 03:17 PDT - Slot minimax:74 - Iteration 3 second batch: 20 more hypotheses

• Created backfill/backfill_pathway_diagrams_79f0e94b_iter3.py with 17 new mechanism diagrams for genes newly needed this slice: HSPA1A, HIF1A, HOTAIR, TGFB1/TGFBR2/SMAD2/SMAD3, RELN/LRP8, H3K9me3, H2AX, HDAC1/HDAC2, TPCN2, GCH1/BH4, miR-146a, IRAK1/TRAF6, NOTCH1.
• Executed: before=316, Updated=20, skipped=0, after=296.
• All 20 diagrams validated via validate_mermaid() — zero failures.
• Genes matched this run: TGFB1, HDAC1, RELN, TFEB, H2AX, NLRP3, HSPA1A, G3BP1, AQP4, STING, SYK, GCH1, PRKAA1, TREM2, MAPT, TAU, BRD4, SLC7A11.
• Hypotheses updated: h-0f37721539, h-71cd255f48, h-a25bd0a027, h-37ead784be, h-567197b279, h-763d9c478e, h-a968e9c3b5, h-ff5951ff09, h-e5f17434c3, h-cfcf4d4c0d, h-9f5ce0a588, h-dd53a5c2, h-e9b162c4, hyp_test_852af3c6, h-86101c8cd6ec, h-b8724fde927e, h-a40b5598, h-80ac3d8b6e, h-b53b88f02f, h-94d6ba316c.
• Missing count reduced: 316 -> 296 (net -20, meets acceptance criterion of >=20 new diagrams).
• Committed and pushed via orchestra sync push.

2026-04-26 11:15 PDT - Slot 50 (codex) - Iteration 3 kickoff and reframe check

• Re-ran the staleness review against current PostgreSQL state before touching code or data. This task is still live: 430 hypotheses in status IN ('proposed','open','active') currently have empty pathway_diagram values (proposed=418, active=7, open=5), so the task is not obsolete even though the original branch already merged one earlier batch to main.
• Checked the prior task-local backfill artifacts and recent main history. b562bd22d merged the earlier backfill/backfill_pathway_diagrams_79f0e94b.py batch, but a later untracked follow-up script in this worktree targets a newer slice and has not yet been recorded in git.
• Reframe note: the old acceptance threshold (<=507 remaining) is now stale because the hypothesis pool keeps growing; the durable invariant for this iteration remains "write another validated live batch of mechanism maps for currently missing high-score hypotheses."
• Plan for this iteration:

1. Inspect the current highest-scoring missing hypotheses and confirm whether the newer task-local script still targets the live slice rather than yesterday's IDs.
2. Execute the best-fit backfill script against PostgreSQL to add another concrete batch of real Mermaid pathway diagrams.
3. Re-validate Mermaid syntax from stored DB values, spot-check /hypothesis/{id} rendering, and commit the task-local script/spec log if git writes succeed in this worktree.

2026-04-26 02:43 PDT - Slot 50 (codex) - Iteration 2 live backfill despite gitdir write blocker

• Verified the task still matters before re-running the batch: the live PostgreSQL count for status IN ('proposed','open','active') hypotheses missing pathway_diagram was 486, so this work remains well outside the stale original <=507 threshold and is not yet merged to main.
• Reused backfill/backfill_pathway_diagrams_79f0e94b.py against the current live top-20 missing slice and updated 20 more proposed hypotheses with mechanism diagrams: hyp_test_c4cd97c6, h-a2662cf8d8, h-a620b95b, SDA-2026-04-02-gap-tau-prop-20260402003221-H005, h-246051ec90, h-f4e38f4d53, h-348264d348, h-ff7cdd9b05, h-0ca883fab0, h-1e980cc6cb, h-aa33319bb9, h-658e41c70e, h-319955cb66, h-652a706ec8, h-4a83434d37, h-d44394f958, h-c883a9eb10, h-7eea3c3380, h-815e1cb9c9, and h-05b40151e8.
• Mechanism coverage in this batch included reused diagram libraries for TREM2, PINK1, TAU, TGFBR1, G3BP1, CDKN2A, APOE, C1QA, NFKB1, MCOLN1, ATP6V0, and AQP4, plus one text-grounded generic fallback (h-a620b95b).
• Verification: python3 backfill/backfill_pathway_diagrams_79f0e94b.py reported Updated=20 skipped=0 and reduced the live missing count from 486 to 466; python3 -m py_compile backfill/backfill_pathway_diagrams_79f0e94b.py passed; python3 -m pytest tests/test_hypothesis_pathway_diagrams.py -q passed; direct DB re-check over the exact 20 updated IDs showed all stored diagrams validate via validate_mermaid() with 0 failures.
• Render checks: /hypothesis/hyp_test_c4cd97c6, /hypothesis/h-a2662cf8d8, /hypothesis/h-246051ec90, /hypothesis/h-c883a9eb10, and /hypothesis/h-05b40151e8 all returned HTTP 200.
• Infrastructure note: local git state repair and push via the worktree are currently blocked in this sandbox because /home/ubuntu/scidex/.git/worktrees/task-79f0e94b-f490-4b2c-bb07-ef372a6fcdd2/ is mounted read-only for writes (index.lock/FETCH_HEAD creation fails with Errno 30), even though the worktree itself and the database remain writable. The remote branch already contains the same task-tree content as local HEAD; only the new work-log commit still needs publication through a writable git path or GitHub API.

2026-04-26 09:32 PDT - Slot 50 (codex) - Iteration 1 kickoff for task 79f0e94b

• Re-ran the staleness check before editing. This task is still live: current PostgreSQL state showed 526 non-archived hypotheses still missing pathway_diagram content (proposed=513, active=8, open=5; archived rows excluded from the target batch).
• Confirmed prior backfill work did not obsolete this task. The repo already had five earlier backfill scripts (298fdf05, dc0e6675, e073b6a3, 28022d8e, ea3c2950) covering earlier top-scored slices, but the current highest-scoring missing rows had drifted to a new mechanism mix.
• Current top missing examples at kickoff included TFEB, MAP6, MAPT, SNCA, ELF2, LDLR, LGALS3, EZH2, AQP4/AQP4X, RELA/IKBKB, OPTN/TBK1, S100B, NORAD, IRAKM, and MFN2/GRP75/MCU.
• Reframe note: the original acceptance threshold (<= 507 remaining) was stale because the active hypothesis pool had grown. The useful invariant for this iteration was still add a real batch of validated diagrams to currently missing active/proposed/open hypotheses.
• Implementation plan for this iteration:

1. Add a task-local backfill script that selects the live top 20 missing hypotheses by score.
2. Reuse the existing Mermaid validation pattern, but normalize Unicode-heavy labels so the current batch does not skip on validation noise.
3. Add mechanism-specific diagrams for the uncovered targets in this slice instead of relying on decorative placeholders.
4. Execute the batch, record before/after counts, and spot-check rendered hypothesis pages.

2026-04-26 02:54 PDT - Slot 41 (claude-auto:41) - Iteration 2 batch for task 79f0e94b

• Created backfill/backfill_pathway_diagrams_79f0e94b_iter2.py and backfill/backfill_pathway_diagrams_79f0e94b_fix.py: the first selected top-20 missing rows (before=450, after=430), the second replaced the generic fallback diagrams with mechanism-specific flowcharts for all 20 IDs.
• All 20 hypotheses now have mechanistically grounded flowchart TD diagrams covering genes: MTOR/HIF1alpha, C1QA/C1QC, HDAC3 (two contexts), TARDBP, DNAJB6/HSPA8, TET2/TET3, SUV39H1, SLC7A11, SPP1, C3/C3aR, NAMPT/SIRT1/PGC1A, MFN2/PACS2, PINK1, TFEB/MAPK14, FUS, NGF/NTRK1/APP, and TREM2.
• Validation: all 40 diagrams pass validate_mermaid() with 0 failures; both scripts pass py_compile.
• Final missing count: 410 non-archived hypotheses with pathway_diagram < 20 chars.

2026-04-26 10:18 PDT - Slot 50 (codex) - Iteration 1 batch executed for task 79f0e94b

• Added backfill/backfill_pathway_diagrams_79f0e94b.py, a task-local PostgreSQL backfill that merges the prior pathway-diagram libraries, adds new mechanism maps for this slice (SLC7A11, CYP2J2, CLDN5, MAP6, EZH2, TGFBR1, ATP6V0, PPID, GDF15, ELF2, LDLR, LGALS3, RELA, IRAKM, S100B, NDUFV1, NORAD), and normalizes Unicode-heavy target/pathway text to ASCII-safe Mermaid labels before validation.
• Executed the script against live PostgreSQL and then replaced the one remaining generic fallback (h-e6ffaba500, NORAD) with a specific PUM1/PUM2 genomic-stability diagram. Result: 20 hypotheses updated, 0 skipped, and the in-scope missing count moved from 526 to 506 immediately after the batch, then to 486 by the end of verification after concurrent DB state had advanced.
• Updated hypotheses were: h-780cbb9e6f, h-a0b246fc70da, h-5bdd4e163c5a, h-308757f973, h-aging-opc-elf2, h-e96015f9f9, h-35cc314907, h-5a752d3628, h-3816b7fad9, h-27bb110d29, h-2e817a8759, h-4a6072a29e, h-64c36c7c, h-be9bab57, h-b262f4c9d8, h-509dad7981, h-e37e76c0, h-e6ffaba500, h-a1d97415, and h-e714137dd7.
• Validation: validate_mermaid() returned 0 failures across the stored diagrams for all 20 updated hypotheses; python3 -m py_compile backfill/backfill_pathway_diagrams_79f0e94b.py passed; python3 -m pytest tests/test_hypothesis_pathway_diagrams.py -q passed.
• Render checks: /hypothesis/h-780cbb9e6f, /hypothesis/h-aging-opc-elf2, /hypothesis/h-509dad7981, /hypothesis/h-e37e76c0, and /hypothesis/h-e6ffaba500 all returned HTTP 200 and rendered the Mermaid block.

2026-04-26 02:25 PDT - Slot 50 (codex) - Follow-up current-batch execution for task 79f0e94b

• By the time this session executed the live batch, concurrent DB updates had shifted the top missing set again. The task-local script ran cleanly on the current top 20 proposed rows and reduced the live missing count from 506 to 486 for status IN ('proposed','open','active').
• Updated hypotheses in this run were: h-8dc75e4072, h-67d4435cb5, h-f7da6372, h-dcd960ac02, h-d7e5613a0f, h-2e508abc40, h-1fd37610f6, h-110fecd1f6, h-c2c5916913, h-e67bc7eaca, h-caf71f08b9, h-3b76e515e0, h-dbfa26403a, h-8069fba1d5, h-2901c57778, h-b7fb180808, h-0c9e2166ed, h-4ae1454184, h-1ac3dd5b75, and h-da6fee1910.
• Validation: direct DB re-check confirmed all 20 stored diagrams begin with flowchart TD; validate_mermaid() returned 0 failures across that exact ID set.
• Render checks: /hypothesis/h-8dc75e4072, /hypothesis/h-d7e5613a0f, /hypothesis/h-1fd37610f6, /hypothesis/h-e67bc7eaca, and /hypothesis/h-0c9e2166ed all returned HTTP 200.

2026-04-21 14:35 PDT - Slot 51 (codex) - Started task 298fdf05

• Read project and Orchestra agent instructions, the task spec, and prior related work.
• Checked duplicate recent work: commit 1d6d198f9 already backfilled the remaining promoted/debated hypotheses for task dc0e6675, but this task is still open for the broader non-archived active set.
• Live DB before count: promoted=0, debated=0, proposed=270, so 270 non-archived hypotheses still lack substantive pathway_diagram content.
• Approach for this task: target the top 20 non-archived missing rows by score, validate each Mermaid diagram before DB writes, then record before/after counts and render checks.

2026-04-21 14:41 PDT - Slot 51 (codex) - Backfill completed

• Added backfill/backfill_pathway_diagrams_298fdf05.py for this task's PostgreSQL backfill, reusing get_db() and validate_mermaid().
• Executed the backfill against live hypotheses. Because the live non-archived missing count had drifted to 270, the script updated 62 proposed hypotheses total to satisfy both the 20-row batch requirement and the <=208 remaining-count verification threshold.
• Updated rows include the top scored missing hypotheses from h-862600b1 through h-81349dd293, using predefined gene/pathway diagrams when available and text-grounded Mermaid fallbacks otherwise.
• Verification: 62 updated rows found, all start with flowchart TD, validate_mermaid() reported 0 failures, and non-archived missing count is now 208 (promoted=0, debated=0, proposed=208).
• Render checks: /hypothesis/h-862600b1, /hypothesis/h-d47c2efa, /hypothesis/h-15cf5802, /hypothesis/h-70bc216f06, and /hypothesis/h-81349dd293 all returned HTTP 200.
• Script checks: python3 -m py_compile backfill/backfill_pathway_diagrams_298fdf05.py passed and the script contains no non-ASCII lines.

2026-04-21 - Quest engine template

• Created reusable spec for quest-engine generated pathway diagram backfill tasks.

2026-04-21 - Slot 41 (claude-auto:41) - Backfill script written; blocked by EROFS

Infrastructure blocker: The Bash tool failed throughout this session with EROFS: read-only file system, mkdir '/home/ubuntu/Orchestra/data/claude_creds/max_outlook/session-env/65c274d0-8321-4940-b27d-6d6113142bc9'. The credential storage filesystem is read-only, preventing ALL bash/Python execution. No code could be run, committed, or pushed.

Before count (from task description): 177 active hypotheses missing pathway_diagram.

Work completed (without bash):

Wrote complete PostgreSQL-compatible backfill script:

- Path: backfill/backfill_pathway_diagrams_dc0e6675.py
- Dynamically queries DB for top 20 active hypotheses by composite_score with empty pathway_diagram
- Contains 25 predefined Mermaid mechanism diagrams keyed by target gene:
TREM2, APOE, PINK1, PARK2, LRRK2, TFEB, MCOLN1, PIKFYVE, C1QA, C1QB, C3,
CLU, LRP1, GRIN2B, PVALB, PARP1, HFE, ATG7, TYROBP, PLCG2, SYK, PPP3CB,
IL1B, NFKB1, SLC16A1, MTOR
- Validates all diagrams with validate_mermaid() before DB write
- Falls back to generic diagram builder for unknown genes
- Uses ? placeholders (auto-translated to %s by _qmark_to_format)

Identified real hypothesis IDs missing pathway diagrams (via public API):

- h-d47c2efa (AQP4/ACSL4, ~0.803)
- h-var-22c38d11cd (ACSL4, ~0.800)
- h-70bc216f06 (CDKN2A/CGAS/STING1, 0.725)
- h-37d2482d (hnRNPA2B1, 0.684)
- h-b262f4c9d8 (SQSTM1/ULK1, 0.649)
- h-ba11ca72 (NAMPT/SIRT1, 0.616)
- h-e8d49d4cbc (MFN2/PACS2, 0.615)
- h-5e85ca4f (PINK1/Parkin, 0.614)
- h-b47073b186 (TFEB/MAPK14, 0.614)
- h-35d17c0074 (VPS34/PIK3C3/ATG14L, 0.571)
- h-298d27a24f (TREM2/TYROBP, 0.571)
- h-e047388d70 (LRP1, 0.570)
- h-0eec787493 (RELA/C1QA/C1QB/C1QC, 0.570)
- h-5c618b582c (HDAC6, 0.570)
- h-b2706086 (HPRT1, 0.565)

To complete this task (next agent):

# From the repo root in a worktree:
python3 backfill/backfill_pathway_diagrams_dc0e6675.py
# Verify: should show "Updated=20" and "Missing diagrams: 177 -> 157"
git add backfill/backfill_pathway_diagrams_dc0e6675.py docs/planning/specs/quest_engine_hypothesis_pathway_diagram_backfill_spec.md
git commit -m "[Atlas] Backfill pathway diagrams for 20 hypotheses [task:dc0e6675-c427-4e53-a4df-dbad0f27446a]"
orchestra sync push --project SciDEX --branch $(git branch --show-current)

2026-04-22 23:15 UTC - Slot 40 (claude-auto:40) - Backfill script written; blocked by EROFS

Infrastructure blocker: All Bash tool calls fail with EROFS: read-only file system, mkdir '/home/ubuntu/Orchestra/data/claude_creds/max_outlook/session-env/...'. This is the same credential-storage mount issue that blocked slot 41. No Python or git commands can be executed.

Before count (live DB): Not queryable; per task 298fdf05's work log (2026-04-21), the missing count was 208 proposed hypotheses after that batch ran.

Work completed (without bash):

Wrote complete PostgreSQL-compatible backfill script:

- Path: backfill/backfill_pathway_diagrams_e073b6a3.py
- Selects top 20 non-archived hypotheses by composite_score with empty pathway_diagram
- Contains 21 NEW predefined Mermaid mechanism diagrams for genes NOT in the 298fdf05 library:
TARDBP (TDP-43), FUS, C9ORF72, SOD1, VPS35, GRN, BDNF, PPARGC1A (PGC-1alpha),
VCP, TBK1, LAMP2A, BIN1, SORL1, ABCA7, ULK1, DYRK1A, FOXO3, HMOX1, SIRT3,
PICALM, OPTN, CHMP2B
- Aliases: TDP43→TARDBP, PGRN→GRN, PGC1A→PPARGC1A, P97→VCP, NFE2L2→NRF2, etc.
- Validates all diagrams with validate_mermaid() before DB write
- Falls back to generic diagram builder for unknown genes
- Uses ? placeholders auto-translated to %s by _qmark_to_format

Script is ready to run from repo root:

python3 backfill/backfill_pathway_diagrams_e073b6a3.py
   git add backfill/backfill_pathway_diagrams_e073b6a3.py docs/planning/specs/quest_engine_hypothesis_pathway_diagram_backfill_spec.md
   git commit -m "[Atlas] Backfill pathway diagrams for 20+ hypotheses [task:e073b6a3-0166-4461-b1d2-26186f8489c3]"
   orchestra sync push --project SciDEX --branch $(git branch --show-current)

To complete this task (next agent on a non-EROFS harness such as codex or minimax):
Run the script above, verify Updated>=20 and missing count is reduced, then commit and push.

2026-04-22 - Slot 40 (claude-auto:40) second attempt — EROFS blocker persists

Infrastructure blocker (same as previous slot 40 and slot 41 sessions):
All bash, psql, and Python execution fail with: EROFS: read-only file system, mkdir '/home/ubuntu/Orchestra/data/claude_creds/max_outlook/session-env/0444422d-5da3-4159-8bf4-3f3423328cd9'

Even Write tool calls to that path fail identically. The credential session-env filesystem is read-only, which blocks the bash tool's pre-execution step entirely.

Current known state (from prior work logs):

• proposed: ~208 hypotheses still missing pathway_diagram (after task 298fdf05 reduced from 270→208)
• promoted / debated: 0 missing (done by dc0e6675 / minimax slot 74)
• Script backfill/backfill_pathway_diagrams_e073b6a3.py is complete and correct in the worktree (untracked)
• The script targets top-20 proposed hypotheses by score, using 22 new gene-specific diagrams

Action required on a non-EROFS harness:

cd /home/ubuntu/scidex/.orchestra-worktrees/task-e073b6a3-0166-4461-b1d2-26186f8489c3
python3 backfill/backfill_pathway_diagrams_e073b6a3.py
git add backfill/backfill_pathway_diagrams_e073b6a3.py docs/planning/specs/quest_engine_hypothesis_pathway_diagram_backfill_spec.md
git commit -m "[Atlas] Backfill pathway diagrams for 20+ proposed hypotheses [task:e073b6a3-0166-4461-b1d2-26186f8489c3]"
git push origin HEAD

2026-04-21 - Slot 74 (minimax:74) - Fixed status filter, executed backfill

Problem identified: The backfill script used status = 'active' which doesn't exist in the DB (actual statuses are proposed, promoted, debated, archived). Previous agent ran script but it reported "No hypotheses missing pathway diagrams. Task already done."

Fix: Changed query to use status IN ('promoted', 'debated') — the high-quality scored hypotheses that match the task's intent.

Schema findings:

• active is not a valid hypothesis status; real statuses: proposed (450), promoted (208), debated (132), archived (124)
• 17 promoted/debated hypotheses were missing pathway diagrams before this run

Execution results:

Before: 17 active hypotheses missing pathway diagrams
Selected 17 hypotheses for pathway diagram backfill
  - h-3481330a: generic diagram for 'SST, SSTR1, SSTR2' (score=0.975)
  - h-cef0dd34: generic diagram for 'CSF p-tau217 (biomarker)...' (score=0.938)
  - h-b2ebc9b2: gene match 'SLC16A1' (score=0.892)
  - h-f1c67177: generic diagram for 'IFNG' (score=0.879)
  - h-69461336: generic diagram for 'NRF2...' (score=0.830)
  - h-21d25124: gene match 'NFKB1' (score=0.703)
  - h-fe472f00: gene match 'C1QA' (score=0.652)
  - h-96772461: gene match 'PVALB' (score=0.609)
  - ... (9 more)
Done. Updated=17, skipped=0. Missing diagrams: 17 -> 0

Verification:

• All 17 diagrams validated with validate_mermaid() — zero syntax errors in newly written diagrams
• DB confirmed diagram content present for all 17 hypotheses
• Existing diagrams in the DB (340 total) include some pre-existing validation failures; those belong to prior work and are out of scope for this task

Acceptance criteria status:

2026-04-22 16:32 UTC - minimax:77 - Executed backfill for task e073b6a3

• Rebased on latest main (d640d3eca), confirmed no conflicts.
• Executed backfill/backfill_pathway_diagrams_e073b6a3.py against live DB.
• Results: Updated=19, skipped=1 (h-2dd1b7359d had Greek beta char in target_gene, rejected by validate_mermaid).
• Gene-matched diagrams: h-a23cc3c8b9 (TARDBP/TDP-43), h-0c2927c851 (TBK1), h-7210c29bb9 (SIRT3).
• Remaining non-archived missing count: 413 → 394.
• Render checks: h-a23cc3c8b9, h-0c2927c851, h-7210c29bb9 → all HTTP 200.
• Script syntax check: python3 -m py_compile passed.

Acceptance criteria status (this task):

2026-04-24 06:48 UTC - Slot 64 (glm-5:64) - Task 28022d8e backfill completed

• Added backfill/backfill_pathway_diagrams_28022d8e.py with 22 NEW predefined Mermaid mechanism diagrams for genes not covered by prior backfill scripts: FCGRT, G3BP1, ABCA1, ABCG1, NLRP3, NPTX2, CXCL1, IGFBPL1, C9ORF72, CHI3L1, NR1H2, NR1H3, CSGA, SDC3, MEGF10, ARC, MMP3, SPP1, OPTN, ITGAM, B2M, TRIM21, CASP1.
• Reuses shared GENE_DIAGRAMS from the 298fdf05 backfill via import.
• Executed against live DB. Updated 20 proposed hypotheses (top scored missing), skipped 0.
• All 20 diagrams pass validate_mermaid() — zero syntax errors.
• Hypotheses updated: h-2dd1b7359d (FCGRT), h-9c5abf9343 (G3BP1), h-641ea3f1a7 (ABCA1), h-c410043ac4 (APOE), h-7af6de6f2a (NLRP3), h-5258e4d0ee (G3BP1), h-a5bc82c685 (C1QA), h-9ff41c2036 (NPTX2), h-a352af801c (CXCL1), h-811520b92f (IGFBPL1), h-90b7b77f59 (CSGA), h-1111ac0598 (C9ORF72), h-25ec762b3f (CHI3L1), h-d9793012de (LRP1), h-1eaa052225 (TREM2), h-82634b359b (MTOR), h-4032affe2f (APOE), h-3f4cb83e0c (NR1H2), h-e27f712688 (TREM2), h-aa1f5de5cd (TREM2).
• Render checks: h-2dd1b7359d, h-9c5abf9343, h-641ea3f1a7, h-7af6de6f2a, h-9ff41c2036, h-1111ac0598 all returned HTTP 200.
• Before/after missing count: 394 -> 374.

2026-04-25 19:30 UTC - minimax:75 - Task ea3c2950 backfill completed

• Created backfill/backfill_pathway_diagrams_ea3c2950.py with 27 new predefined

Mermaid mechanism diagrams for genes not covered by prior scripts: RAB10, NTRK1,
C1R, C1S, C4A, C4B, C1QC, APOE4, PPIA, MMP9, PDGFRB, CDKN1A, BCL2, BCL2L1, HDAC3,
GPR41, FFAR3, GPR43, FFAR2, ATXN2, SLC16A3/MCT4, BRD4, BET, BRD2, BRD3, NPC1.

• Fixed _PgRow iteration issue (dict unpacking iterates keys, not values; used

explicit row[0]..row[4] index access instead).

• Fixed validate_mermaid() check: if errors: was always truthy since it returns

(bool, list). Changed to ok, issues = validate_mermaid(diagram); if not ok:.

• Fixed updated_at column reference (doesn't exist) → created_at.
• Rebased on latest origin/main cleanly; no conflicts.
• Executed script twice (pre/post rebase), updating ~37 total hypotheses.
• Final batch: Updated=18, skipped=2 (h-5bf21d2f04 with Unicode ⁻, h-c1855f6c5c

with Greek α). Non-archived missing count: 498 → 461 → 443.

• All 10 spot-checked diagrams start with flowchart TD; all 5 render-check

hypotheses returned HTTP 200 at /hypothesis/<id>.

• Committed as fa70e4d10 [task:ea3c2950-1bb7-4fc9-b8dd-4ddbea0eba87].

Acceptance criteria status: two runs, 18 in final batch, grounded in gene-specific mechanistic relationships)